Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease.

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF 23, fetuin-A, sclerostin, and VC scores (Adragao method). Prevalence of VC was similar in both groups, but HD patients had more frequent VC scores ≥ 6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A and sclerostin levels were higher in pre-HD, while FGF 23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin, and no vitamin D treatment, while in HD patients with higher sclerostin, FGF 23 and urea, and lower iPTH. Conclusion: Biomarkers could be measurable indicators of biological processes underlying VC in CKD patients that may serve as a potential guide for considering personalized therapeutic approaches. Further studies are needed to elucidate the underlying pathways.

Significance of acPWV for Survival of Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Abnormal arterial stiffness (AS) is a major complication in end-stage kidney disease (ESKD) patients treated by dialysis. Our study aimed to determine the significance of AS for survival of prevalent dialysis patients, as well as its association with cardiovascular parameters or vascular calcification promoters/inhibitors or both and AS. MATERIALS AND METHODS: The study involved 80 adult hemodialysis patients. Besides standard laboratory analyses, we also determined promoters and inhibitors of vascular calcification (bone biomarkers): serum levels of fibroblast growth factor 23 (FGF23), soluble Klotho, intact parathormone (iPTH), 1,25-dihydroxyvitamin D3, osteoprotegerin, sclerostin, AS measured as ankle carotid pulse wave velocity (acPWV), Ankle Brachial Index (ABI), and vascular calcification (VC) score. Patients were monitored for up to 28 months. According to the median acPWV value, we divided patients into a group with acPWV ≤ 8.8 m/s, and a group with acPWV > 8.8 m/s, and the two groups were compared. RESULTS: Values for bone biomarkers were similar in both groups. Mean arterial blood pressure (MAP), central systolic and diastolic brachial blood pressure, heart rate, and pulse pressure were higher in the group with acPWV > 8.8 m/s than in the group with acPWV ≤ 8.8 m/s. The mortality was higher for patients with acPWV > 8.8 m/s at any given time over 28 months of follow-up. In multivariable analysis, predictors of higher acPWV were age >60.5, higher pulse rate, and higher central systolic or brachial diastolic blood pressure. CONCLUSIONS: According to our results, we advise the measurement of acPWV preferentially in younger dialysis patients for prognosis, as well as intervention planning before the development of irreversible changes in blood vessels. In addition, measuring central systolic blood pressure seems to be useful for monitoring AS in prevalent hemodialysis patients.

Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia.

Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L-carnitine and L-acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a therapeutic formulation, Proxeed Plus, on sperm parameters in oligoasthenozoospermic men. This prospective, randomised, double-blind, placebo-controlled clinical trial involved 175 males (19-44 years) with idiopathic oligoasthenozoospermia who failed to impregnate their partners (12 months). Males received Proxeed Plus or placebo for 3 and 6 months. Sperm volume, progressive motility and vitality significantly (p < 0.001) improved after 6 months compared to baseline. Sperm DNA fragmentation index significantly decreased compared to baseline (p < 0.001) and the 3-month therapy (p = 0.014) in treated men. Increased seminal carnitine and α-glucosidase concentration also positively correlated with improved progressive motility. Decreased DNA fragmentation index was the good predictor of progressive sperm motility >10%, and simultaneous measurement of changes in sperm vitality and DNA fragmentation index gave the highest probability of sperm motility 10% (AUC = 0.924; 95% CI = 0.852-0.996; p < 0.001). Logistic regression analyses revealed DNA fragmentation index decrease as the only independent predictor of sperm motility 10% (OR = 1.106; p = 0.034). We have demonstrated the beneficial effects of carnitine derivatives on progressive motility, vitality and sperm DNA fragmentation. Combining metabolic and micronutritive factors is beneficial for male infertility.

Dual Roles of the Mineral Metabolism Disorders Biomarkers in Prevalent Hemodilysis Patients: In Renal Bone Disease and in Vascular Calcification.

BACKGROUND: Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months). METHODS: Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured. RESULTS: VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007-1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992-1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000-0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059-0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325-39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient's age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk. CONCLUSIONS: Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.

Epidural anesthesia can block the negative effects of prostaglandin mediators during prostate surgery.

INTRODUCTION: Inflammation plays a key role in the development of benign prostatic hyperplasia. Prostaglandin E2 (PGE2) is an important inflammation factor found in enlarged prostatic tissue that can be the main cause of inflammatory pain. The aim of this study was to investigate whether epidural anesthesia can block the negative effects of prostaglandin mediators during prostate surgery. MATERIALS AND METHODS: The study included 60 patients who underwent open prostatectomy. All patients were randomly allocated to one of two study groups. The first group received general anesthesia and the second group a combination of general and epidural anesthesia. Main outcome measures were plasma concentration of PGE2, adrenaline, noradrenaline, and dopamine, before induction of anesthesia and at the time of enucleation. RESULTS: Preoperative serum concentrations of PGE2 were high in both groups. During enucleation, serum concentrations of adrenaline, noradrenaline, and dopamine increased, followed by a rise of systolic and diastolic blood pressure in the group of patients that received only general anesthesia. Serum concentration of PGE2 was at the same level as before induction of anesthesia in both groups. CONCLUSION: Epidural anesthesia blocks transmission of painful stimulus through the spinal cord caused by prostaglandin release and prevents the rise of catecholamines and blood pressure. Open prostatectomy can become a safer procedure performed under a combination of general and epidural anesthesia. Negative intraoperative effects of inflammatory prostate mediators during other techniques for prostate surgery could also be blocked with epidural anesthesia.

The correlation of biochemical and morphologic parameters in the assessment of sperm maturity.

OBJECTIVE: To examine the relationship between biochemical markers and morphologic sperm characteristics, including head, neck, and tail changes. METHODS: The study evaluated 154 patients who went to the Andrology Laboratory of the Clinic of Urology, Clinical Center of Serbia. Patients were divided into 4 groups: normozoospermic, oligozoospermic, severe oligozoospermic, and asthenozoospermic, according to the sperm concentration and motility. RESULTS: The differences in creatine kinase (CK) and CK-M levels between normozoospermic and the 2 groups of oligozoospermic patients were significantly different (P <.01). The CK and CK-M levels correlated negatively with sperm concentration and sperm motility, but correlated positively with the pathologic sperm form. Patients with CK values >0.093 have a total number of pathologic forms higher than 0.40 (87.5% sensitivity, 77.3% specificity, the area under the curve was 0.832, P <.001). Patients with CK values <0.09 U/L have normal spermatogenesis and pathologic disorder of the head <15%, neck <12%, and tail <10%. CONCLUSION: The relation between sperm morphology and biochemical markers included in the maturation process is established during the sperm genesis process. If the results of these markers are used together with the morphology of the spermatozoa in the interpretation of infertility, it would lead us to better insight of the fertility potential of the each patient.

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

INTRODUCTION: Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. MATERIALS AND METHODS: From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV < 31 mL and TPV ≥ 31 mL. Additional three groups were formed upon MTOPS study criteria: non- progressive BPH group (TPV < 31 mL, PSA < 1.6 ng/mL, age < 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV ≥ 31 ml, PSA ≥ 1.6 ng/mL, age ≥ 62 yrs). RESULTS: Average uPSA values in the groups TPV < 31 mL and TPV ≥ 31 mL were 119.3 ± 124.5 and 255.5 ± 204.9 ng/mL, respectively and they were significantly different (p < 0.0001). Average uPSA values in the non- progressive BPH group, intermediate group and progressive BPH group were 86.8 ± 82.4 ng/mL, 166.6 ± 164.9 ng/mL and 274.9 ± 208.3 ng/mL, respectively and they were significantly different (p < 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p < 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. CONCLUSION: The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

Glycosaminoglycans in the urinary bladder mucosa, tumor tissue and mucosal tissue around tumor.

INTRODUCTION/AIM: Glycosaminoglycans (GAG) are one of the main constituents of the connective tissue and cellular membrane. Their presence has been evidenced in mucosa and muscular tissue of the urinary bladder of both healthy individuals and those affected by carcinoma. This suggest their potential role in the onset of bladder carcinoma and follow-up of those patients. The aim of the study was to determine GAG levels in tumor tissue and the surrounding bladder mucosa in patients with bladder tumor, as well as in the bladder mucosa in patients with bladder carcinoma, and to compare the results according to the grade and stage of tumor and relapse. METHODS: Tissue samples were taken in 61 patients (48 males and 13 females), mean age 61.5 years, range 40-92 years, obtained by transurethral resection (TUR) of bladder tumor, and 8 healthy persons. Determination of a total GAG content in the tissue samples was done by the Whiteman's method and then compared regarding the tumor grade and stage. RESULTS: Tumor grade and stage directly correlated with the levels of GAG. The GAG levels were significantly higher in tumor samples as compared to healthy mucosa. CONCLUSION: Higher GAG levels were recorded in all the patients with bladder tumors comparing to samples obtained from healthy individuals. GAG levels do not predict tumor relapse.

[The effect of urinary tract calculosis to levels of low molecular inhibitors of crystallization in the urine].

The incidence of urinary tract calculosis continuously progresses. The triggering event in the process of stone formation is decreased urinary level of crystallizing inhibitors. The aim of our study was to investigate whether the existing stone or applied therapeutic procedure - extracorporeal shock waves lithotripsy (ESWL) - has effect to urinary levels of Mg, citrate and pyrophosphate. Study included 128 patients with the upper urinary tract stones. ESWL using the Lithostar (Siemens) device was used as a mode of treatment. Out of all patients, 76 (59%) were free of stone particles before 1 month, while 52 (41%) had residual stone fragments even 3 months after ESWL. Mg, citrate and pyrophosphate were measured in 24h-urine specimens: before, between days 2 and 3, as well as 1 and 3 months after ESWL. The analysis of the results revealed that stone itself had no effect on urinary crystallizing inhibitors. Detected increased urinary levels of Mg, citrate and pyrophosphate after ESWL, compared with pre-treatment values, could be attributed to applied therapeutic procedure.